title: Functional relevance of D,L-sulforaphane-mediated induction of vimentin and plasminogen activator inhibitor-1 in human prostate cancer cells.
abstract: OBJECTIVE
  D,L-Sulforaphane (SFN) is a promising chemopreventive agent with in vivo efficacy against prostate cancer in experimental rodents. This study was undertaken to determine the role of vimentin and plasminogen activator inhibitor-1 (PAI-1) in anticancer effects of SFN.
  
  
  METHODS
  Effect of SFN on levels of different proteins was determined by Western blotting or immunofluorescence microscopy. RNA interference of vimentin and PAI-1 was achieved by transient transfection. Apoptosis was quantified by flow cytometry. Transwell chambers were used to determine cell migration.
  
  
  RESULTS
  Exposure of PC-3 and DU145 human prostate cancer cells to SFN resulted in induction of vimentin protein, which was accompanied by down-regulation of E-cadherin protein expression. The SFN-mediated induction of vimentin was also observed in a normal human prostate epithelial cell line. RNA interference of vimentin did not have any appreciable effect on early or late apoptosis resulting from SFN exposure. On the other hand, SFN-mediated inhibition of PC-3 and DU145 cell migration was significantly augmented by knockdown of the vimentin protein. Knockdown of vimentin itself was inhibitory against cell migration. The SFN-treated cells also exhibited induction of PAI-1, which is an endogenous inhibitor of urokinase-type plasminogen activator system. Similar to vimentin, PAI-1 knockdown resulted in a modest augmentation of PC-3 cell migration inhibition by SFN. Tumors from SFN-treated transgenic adenocarcinoma of mouse prostate mice showed a 1.7-fold increase in vimentin protein level compared with control tumors.
  
  
  CONCLUSIONS
  The present study indicates that vimentin and PAI-1 inductions confer modest protection against SFN-mediated inhibition of prostate cancer cell migration.
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Avani R
authors.initials: AR
authors.lastname: Vyas
authors.forename: Shivendra V
authors.initials: SV
authors.lastname: Singh
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D015820:Cadherins / Q000037:antagonists & inhibitors / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000819:agonists* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011467:Prostate / Q000187:drug effects / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D034622:RNA Interference; D013454:Sulfoxides; D015854:Up-Regulation / Q000187:drug effects*; D014746:Vimentin / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D015820:Cadherins; D017879:Isothiocyanates; D009363:Neoplasm Proteins; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D013454:Sulfoxides; D014746:Vimentin; C016766:sulforaphane